Pharmacokinetics of o-nitroanisole in Fischer 344 rats
The pharmacokinetics and metabolism of o-nitroanisole (ONA) were studied in male Fischer 344 rats. Three dose levels of ( UC)ONA (5.0, 50, or 500 mg/kg) were administered orally to rats and daily excreta were analyzed for UC. Since the highest dose altered the urinary excretion rate of ONA, a dose of 25 mg/kg was used for subsequent pharmacokinetic studies. Following a single 25 mg/kg iv dose of ( UC)ONA, blood, tissues, and excreta were collected at times ranging from 15 min to 7 days. Urinary excretion accounted for 82% of the dose by 24 hr and 86% by 7 days. Fecal excretion was 7.5% in 24 hr and 9.0% by 7 days. Fifteen min after ONA administration, most of the UC content was found in muscle (20%), skin (10%), adipose tissue (6.8%), and blood (6.5%). The initial elimination t1/2 for UC in all tissues was 1-2 hr and the terminal t1/2 was approximately 4 days. The elimination of parent ONA from blood followed first order biphasic elimination kinetics. Parent ONA was rapidly eliminated from all other tissues in a monophasic manner. Skin and fat demonstrated an uptake phase prior to the elimination of parent. Only 0.5% of the dose was excreted as ONA in the urine. Urinary metabolites of ONA were predominantly conjugated compounds.
- Research Organization:
- Univ. of Arizona, Tucson
- OSTI ID:
- 6232425
- Journal Information:
- Drug Metab. Dispos.; (United States), Journal Name: Drug Metab. Dispos.; (United States) Vol. 5; ISSN DMDSA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ABSORPTION
ADIPOSE TISSUE
ANIMAL TISSUES
ANIMALS
ANISOLE
BILE
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BLOOD
BODY
BODY FLUIDS
CARBON 14 COMPOUNDS
CONNECTIVE TISSUE
ETHERS
FECES
HALF-LIFE
INTESTINAL ABSORPTION
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
METABOLISM
MUSCLES
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PHARMACOLOGY
RATS
RETENTION
RODENTS
TISSUES
UPTAKE
URINE
VERTEBRATES
WASTES